The proposed research will be directed toward study of an experimental model with the aim of gaining better understanding of a translational mechanism whereby hemoglobin alpha chains or alpha chain synthesis appear to modify the rate of synthesis of hemoglobin beta chains. For this purpose an animal model has been devised, employing erythroid cells from a mutant strain or rabbits having hemoglobin alpha chains that contain 3 residues of isoleucine per chain whereas the beta chains contain no isoleucine. By the action of the isoleucine antagonist L-O-methylthreonine alpha chain synthesis can be selectively inhibited allowing the resulting effect on beta chain synthesis to be examined. Previous studies using bone marrow cells from the mutant rabbits demonstrated an inhibition of beta chain synthesis when alpha chain synthesis was reduced. In the next group of experiments we will seek evidence for a definable site of action of the putative control mechanism. These studies will include: 1) Dintzis analysis studies to examine translation in detail; 2) studies of polyribosome distribution; and 3) an examination of chain initiation.